There are reasons to believe that Actinobacillus actinomycetemcomitans (Aa), a gram negative plaque organism, may be linked to the etiology of juvenile periodontitis (JP). In addition to being present in high proportions in the diseased sites of JP patients, Aa produces several potential mediators, among them an endotoxin capable of promoting bone resorption and a leukotoxin capable of killing human PMN and monocytes. Recently, I have observed a non-cytotoxic immune suppressive activity in Aa sonicates. Several investigators have proposed that impaired host defenses may play a pivotala role in susceptibility to periodontal disease in general and JP in particular, it is not unreasonable to propose that this suppressive factor may contribute to the pathogenesis of JP. The aims of this proposal are: 1) to purify and characerize the non-cytotoxic immune-suppressive factor; 2) to determine the mechanism(s) of action of this factor; 3) to determine if this factor acts in vivo to alter lymphocyte responsiveness in experimental animals; and 4) to determine if similar suppressive activity is present in other plaque associated bacteria. For most of these experiments I shall employ human peripheral blood lymphocytes and utilize in vitro assay systems to study the Aa-mediated immune-suppression. I shall also employ an in vivo model system in rabbits (prebiously developed) to examine local as well as systemic effects of the Aa-suppressive factor in lymphocyte responses and cell mediated immunity. These studies will help to clarify the role of Aa in the pathogenesis of JP. The fundamental hypothesis to be tested is that certain plaque associated bacteria may produce factors that cause either local and/or systemic immune suppression, the effects of which might be to enhance their own pathogenicity or that of other opportunistic microorganisms.